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Bispecific therapies targeting CD3, so-called T-cell engagers (TCE), belong to the new spectrum of anti-tumor immunotherapies stimulating T-lymphocytes. TCE are unique constructs targeting the MHC-independent CD3 epsilon subunit (CD3e) and a tumor antigen. To date, only blinatumomab have reached market agreements in lymphoid malignancies with constructs targeting CD3exCD19. Other TCE are in advances development, with promising results targeting CD20 and BSMA in lymphoma and myeloma. These successes have relaunched the development of TCE in solid tumors, bringing mixed results so far (notably in terms of tolerance). Still, TCE pave the way to new immunotherapy in tumors considered to be refractory to inhibitors of immune checkpoints such as prostate cancer or colorectal cancer.

In 2011, 11% of all cancers were diagnosed in people over 85 years old. With the current aging of the French population associated with health progress, we will be confronted more and more frequently with the treatment of very old patients, and this until the horizon 2050, when the population over 75 years old will represent approximately 15% of the total French population (compared to 9.1% in 2015).To understand the management methods for patients over 85 years old with cancer, we carried out an observational study, based on data collected in the OncoPACA-Corse network, with the objective to describe the demographic data of very elderly patients, the characteristics of their pathology and to analyze the therapeutic strategies proposed by oncologists to patients in this population.One thousand three hundred and fifty five cases were analyzed. The mean age of the patients was 88.9 years with 3% of patients over 95 years old and only one was over 100 years old. 51.6% were women. Digestive tumors were the most represented (23.4%), followed by breast tumors (17.7%) and prostate tumors (10.5%), with a diagnosis made at a metastatic stage in 20% of cases. We note that treatment was offered for nearly 85% of patients with a wide range of options, exclusive palliative care was offered in 15% of cases; and whena treatment considered to be not very aggressive, such as hormone therapy, was offered, it seems to be preferred as monotherapy.

The editorial committee of the Bulletin du Cancer is proud to comply with his annual analysis of some of the worldwide updates in oncology that emerge in 2020. We know that all new breakthroughs will not be addressed and apologise for not being comprehensive, but we hope that the topics deciphered herein will bring the reader interesting information in his daily practice in gyneco-oncology, uro-oncology, neuro-oncology, digestive oncology, pneumo-oncology, hemato-oncology, pediatric oncology, or in palliative care.

Over the past years, planet oncology has kept changing and moving forward. Recent results of important clinical trials are challenging our daily practices. With modesty, the Editorial Board of BulletinduCancer has selected some clinical trials they consider as "must-know about" even if they go beyond our medical fields.

Summary Introduction Totally implanted venous access (TIVA) improves the safety and welfare of patients treated with cancer chemotherapy (CCT). We aimed to evaluate patients’ perception of TIVA placement, TIVA use, and information on TIVA, and to assess the association between patients’ perception and their attitude regarding a potential TIVA re-implantation. Methods We conducted a single center cross-sectional survey in a university hospital in Northern France. Patients included were consecutive urologic or digestive cancer inpatients admitted for a CCT cycle via TIVA between April 9th and May 9th 2014. We analyzed patients’ satisfaction, experience, and attitude, especially when requiring potential TIVA re-implantation under local anesthesia (LA), using a standardized questionnaire and medical records. We analyzed risk factors for refusing potential TIVA re-implantation under LA using multivariate logistic regression. Results Eighty-one patients were interviewed (no refusals), including 57 with a TIVA device placed under LA in our university hospital. Among them, 52/57 (91%) reported satisfactory TIVA placement, but respectively 21/57 (37%) and 18/57 (32%) complained of painful or uncomfortable TIVA placement; 51/57 (89%) were satisfied with care provided during CCT cycles. Risk factors for refusing potential re-implantation under LA were: TIVA placement considered painful (P = 0.012) or uncomfortable (P = 0.038) and dissatisfaction with care provided during CCT cycles (P = 0.028). Discussion We show that despite good overall satisfaction regarding TIVA, some aspects were less positive and warrant improvement actions. It suggests that these actions could not only improve patients’ experience of TIVA use but could also facilitate continuation of treatment in the long term.

Adapted physical activity (APA) is recognized as an effective supportive care for asthenia and quality of life in oncology. Before an APA program was organized, the feasibility of such a program was evaluated among the patients.Descriptive, prospective, semi-qualitative, single-center study over a 3-month period in patients treated with ambulatory chemotherapy for digestive cancer. A self-questionnaire was offered to all patients to evaluate their practice and knowledge about APA. In ten patients, fatigue, anxiety and depression were assessed, before and after 9 weeks of hospital-based APA. The scores were compared by matched Student test.Of the 123 patients treated, 80 questionnaires (65%) were exploitable. Before the diagnosis of cancer, 40 patients (50%) were physically active, 20% after (n=16). The reasons for not practicing were: lack of interest/not the idea (42%), lack of time (34%), do not believe in profit (9%), too expensive (8%). Fifty-three patients (66%) were interested in the program. In 10 patients, the APA program significantly reduced the depression score (P=0.024) and a non-significant improvement in anxiety and fatigue.This study shows that patients treated with chemotherapy are unaware of the usefulness of APA and that medical information can improve adherence to such a program. The establishment of an intra-hospital APA program proved to be possible and relevant.

We present and discuss recent data on the frequency of cancer in France and on cancer survival. In the male population, the incidence of prostate and head and neck cancers diminishes rapidly and the incidence of the other common cancers: lung and colorectal diminishes less markedly; cancer mortality decreases for most sites. In the female population, the incidence of breast cancer diminishes rapidly, the incidence of colorectal and uterus cancers diminish less markedly and the incidence of lung cancer increases very fast: the mortality trends are similar. Cancer survival has improved in the last 16 years but some of the improvements are an artifact induced by overdiagnosis.

Poorly differentiated neuroendocrine tumors are rare but their incidence is rising. High-grade neuroendocrine lung tumors, including small-cell lung cancer, are part of this group. Outside of the lung, they most often arise within the gastrointestinal tract (oesophagus, guts and pancreas) and are called neuroendocrine carcinomas. Due to their rarity, very little is known about neuroendocrine carcinomas of the pancreas and the gastrointestinal tract and few studies have been done. Therefore, most therapeutic recommendations are issued from studies on small-cell lung cancers. Histological scores have grown more accurate these past few years: poorly differentiated neuroendocrine tumors regroup various entities such as small-cells, large-cells and mix tumors, which seem to have different prognosis. They are diagnosed at a metastatic state in more than 50 % of cases. In localised disease, surgery is performed on selected patients. Adjuvant chemotherapy is administered in poorly differentiated neuroendocrine tumors of the lung and is an option in neuroendocrine carcinomas, without proof of efficacy. If not operable, radiochemotherapy is done for tumors of the lung, rectum, and eosophagus. If the disease is diagnosed at a metastatic state, chemotherapy is administered with a combination of platin salts (cisplatin or carboplatin) and etoposide. In poorly differentiated neuroendocrine tumors of the lung, prophylactic cranial irradiation is performed in localized disease if there is a good response to chemotherapy. Even if these therapies have improved the overall survival, no improvement has been made during the past four decades and the prognosis remains low.

The squamous cell carcinomas of the upper aerodigestive tracts are frequent neoplasia,with as much as 466,831 and 168,368 cases diagnosed in 2008 among men and women worldwide,respectively. As such, they make up the sixth most frequent neoplasia among men and the eighth among women. Their frequency shows interesting variations covering the last 20 years, with an ascending tendency among women, which is higher in Europe, and a descending tendency in men, maximal in the USA. The comparison with the Belgian official data reveals a striking elevation of incidence of these cancers between both sexes, with important regional differences in Belgium. Finally, when we compare Belgian and French data, these cancers seem more frequent in France in men, but there is an opposite tendency among women, in which the carcinoma of the larynx is most represented in Belgium. Although the limited quality of the data limits the interpretation of these data, they seem to be partly in line with the evolution of the risk factors of these pathologies.

In recent years, long non-coding RNAs (lncRNAs) are emerging as either oncogenes or tumor suppressor genes. Recent evidences suggest that lncRNAs play a very important role in digestive system carcinomas. However, the biological function of lncRNAs in the vast majority of digestive system carcinomas remains unclear. Recently, increasing studies has begun to explore their molecular mechanisms and regulatory networks that they are implicated in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in digestive system carcinomas. It is becoming clear that lncRNAs will be exciting and potentially useful for diagnosis and treatment of digestive system carcinomas, some of these lncRNAs might function as both diagnostic markers and the treatment targets of digestive system carcinomas.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease due to mutations in the tumor suppressor gene STK11. PJS is characterized by periorificial hyperpigmented macules (lentiginosis) and hamartomatous polyposis. Polyps can be located anywhere in the gastrointestinal tract, but are preferably observed in the small bowel (70-90%), the colon (50%) and the stomach (25%). They tend to be cancerous in a particular sequence hamartoma-dysplasia-cancer. The diagnosis is often made in the first or second decade following the appearance of lentigines or upon the occurrence of complications due to polyps (obstruction, intussusception, occult bleeding responsible for anemia). Furthermore PJS is associated with a significant increase in cancer risk (relative risk of 89% over the life according to the most recent series). Digestive cancers are the more frequent with cumulative incidences of 55% for gastro-intestinal cancer (39% for colorectal cancer, 13% for small bowel cancer and between 11 and 36% for pancreatic cancer, respectively). There is also an increased risk of non digestive cancers. In particular the risk of breast cancer is similar to that of patients carrying deleterious BRCA1 or BRCA2 mutations (cumulative incidence of 45%). Gynecological and gonadal tumors are frequent as well and can be more (adenoma malignum) or less aggressive (ovarian sex cord tumors with annular tubules and testicular tumors with calcified Sertoli cells). Finally the frequency of lung cancer is moderately increased. Recommendations for screening and management based on retrospective series in the literature have led to various strategies. The aim of this paper is to summarize the clinical and molecular diagnostic criteria of PJS as well as recommendations on screening strategies, management and monitoring.

This prospective interventional study aims to show the feasibility and impact of information procedure on surrogate and advance directives (AD), for patients with incurable lung or gastrointestinal cancer. The intervention consisted of two semi-structured interviews. The first included: collection of preferences for prognostic information and involvement in decision-making, initial assessment of knowledge, information and surrogate and DA. The second assessed the impact of the first interview on knowledge, surrogate designation and DA writing, the assessment procedure by the patient and assessment of anxiety generated. Among 77 eligible patients, 23 (30 %) were included, 6/29 (21 %) refused to participate, 20/23 (87 %) completed both interviews. Patients not included had a higher 4-month death rate than included ones (39 % vs. 4 %, P=0.002). Patients included had high expectations of information and appreciated it be delivered early, by someone not involved in their care. The study shows the feasibility of the procedure and its impact on the use of surrogate and DA by patients, however, revealing the complexity of approaching end-of-life wills and the importance of a process of anticipated discussion.

Malnutrition is a bad prognostic factor that reduces the quality of life (QoL) in patients with cancer. The objective was to assess the impact of home parenteral nutrition (HPN) on the QoL of elderly malnourished patients with cancer. This French prospective observational study included patients, aged 70 years or older, with cancer, for whom HPN was prescribed for at least 14 days. The patient, the physician and a family member or home caregiver had to fill in a questionnaire at inclusion and 28 days later. Included patients (n = 221) were mainly suffering from a digestive cancer. After HPN intake, improved weight was noticed in 68% and 14% of patients had reached the target weight. Improved global QoL was reported in 59% of patients. Physicians noticed a significant improvement for the same compounds. These results suggest a benefit of the HPN on the nutritional status and QoL in elderly patients with cancer. Further controlled randomised trials are needed to prove the benefit of HPN in the routine management of these patients.

Circulating (CTC) and disseminated tumor cells (DTC) represent two different steps of the metastatic process. As with other types of cancer, the recent development of techniques for the detection of CTC and DTC respectively in the blood and bone marrow of patients generated many results in digestive cancers. However, the interpretation of these results and of the prognostic value of CTC/DTC is often limited by the small cohort size and the heterogeneity of detection methods. The aim of this article is to review the different results and their clinical impact, and discuss the possible use of CTC and DTC as new biomarkers. First of all, it is important to take into account the variability of epithelial markers used for the initial stage of immunoselection of CTC/DTC as well as that of molecular or cytological markers used for the second stage of detection. In esophageal, gastric, pancreatic and hepatocellular carcinomas, and in the ileal and pancreatic neuroendocrine tumors, some studies showed a correlation between the detection of CTC and/or DTC and a clinical pejorative course, whether these tumors were at localized or metastatic stages. On colorectal cancer in the adjuvant setting, a recent meta-analysis showed an association between the detection of CTC in peripheral blood and disease-free survival or overall survival. These results are consistent with those of a study that identified detection of CTC as a prognostic factor for relapse in stage II. This last study concluded that it was necessary to achieve long-term evaluation of CTC as a biomarker to guide the decisions of chemotherapy for stage II. In metastatic colorectal cancer, the FDA approved in 2007 the use of pretherapeutic levels of CTC and its variations per-treatment, determined by CellSearch(®) technology, as a tool in treatments management. However, the modalities of this monitoring have to be specified and clinical benefit or the cost-effectiveness of a treatment based on this new biomarker has to be evaluated. Finally, the qualitative and quantitative monitoring of CTC could be a non-invasive tool to monitor changes in tumor biology throughout the disease, and thereby improve the understanding of the processes of dissemination and therapeutic resistance.

The congress of Asco made the object of numerous summaries of congress made in the heat of the moment and the Bulletin du Cancer decided to ask to his editorial board, a digested summary, at distance of the congress, to try to sum up the data of the congress which are going to change practice. Of the considerable number of communications, editorial board chose 40 communications which appeared to answer these rules. Best understanding of biological mechanisms and new molecules to inhibit targets allow in certain case, to use therapeutic targeting in the true sense. The identification of the gene of fusion EML4-ALK in lung adenocarcinoma, and its inhibition by the crizotinib, constitute a considerable progress for 5% of patients with this disease. Molecular biology with the mutations of the exon 11 in GIST, allow to better define the population which is going to benefit from adjuvant imatinib. In Advanced non-small cell lung cancer, myeloma and advanced lymphoma, maintenance therapy by monoclonal anti-body or inhibitors of tyrosines kinases showed the proof of their effectiveness. In advanced melanoma, ipilimumab is a light of hope in a pathology in always prognostic is so dark. In metastatic adenocarcinoma of the pancreas, there is finally an alternative to gemcitabine with the Folfirinox regimen, with an improvement of overall survival. Biological personalization of cancer treatments is on the road run but the road is still long.

Nutritional management of the cancer patient cannot be ignored, given the well-established links between malnutrition and mortality, postoperative complications, toxicity of radiation and chemotherapy, and quality of life. The expertise of a medical specialist in nutrition is often required given the diversity of the clinical presentation of malnutrition in cancer patients and in certain areas lacking evidence in the literature. In at least some situations, such as for malnourished patients requiring surgery, preoperative nutrition (normally enteral nutrition if possible), is indicated and is also the subject of international recommendations/clinical practice guidelines. The role of the specialist in nutrition is to disseminate such information. There are some situations where the literature offers useful approaches, even if there are no guidelines/recommendations. For example, in disease for which there are not curative therapies but the patient is not yet in a terminal stage, it is legitimate to propose parenteral nutrition in the case of partial bowel obstruction, without waiting for advice from a nutrition specialist. By contrast, his advice is of interest in the ethical discussion which sometimes surrounds decisions to initiate artificial nutrition in patients in the terminal phase. Nutritional recommendations are difficult to formulate for patients with solid tumors on chemotherapy, because there are few data in the literature. The expertise of the specialist in nutrition in this case is most effectively deployed when active treatment of the disease is planned (earlier rather than later in the disease trajectory, in patients responding to treatment for whom further treatment is planned, participants in phase I studies). For cancers of the head and neck preoperative enteral nutrition is recommended for malnourished patients. The literature also provides some practical solutions, even in the absence of well-defined recommendations in some instances. Enteral nutrition is also indicated, without consulting a specialist in nutrition, during radiotherapy when intake falls, to prevent the development of malnutrition. Given the high frequency and important consequences of malnutrition in patients receiving combined radiation and chemotherapy, it is appropriate to initiate enteral nutrition at the 3rd week of treatment. The role of the specialist in nutrition is to interpret the literature and to develop procedures for specific cases.

In oncology, overall survival is often referred to as the gold standard for the evaluation of a novel therapy in phase III clinical trials. The use of an earlier endpoint (intermediate endpoint) would allow to reduce the duration, the number of patients and/or the cost of the studies. Before being used as primary endpoint, it has to be validated as surrogate for overall survival. Two main statistical methods have been developed. The first evaluates the proportion of treatment effect on overall survival that can be attributable to the effect on the surrogate endpoint. The second, the meta-analytic approach, estimates the correlation between the treatment effect on the surrogate and its effect on overall survival, based on the results of previous completed trials. It allows, for a future trial, the prediction of the expected effect on overall survival according to the observed effect on the surrogate. To date, in digestive oncology, only progression-free survival for the treatment of advanced colon cancers and disease-free survival in the adjuvant setting have been validated as surrogate endpoints for overall survival.

The financial orders of French health insurance system for anticancer treatment are guided by the National recommendations of "Good Use" of anticancer treatment (law article dated August 25, 2005 for the good use of anticancer outside the classic financial hospitals). This law of "Good Use" is based on the recommendations of référentiels de bon usage (RBU). RBU include drugs with labelling or protocoles thérapeutiques temporaires (PTT). If the prescriptions do not conform with RBU, it will be considered as not confirmed and the prescriptor has to explain clearly his point of view in the medical file supported by national and international references and publications and also that of the experts' opinions. The objective of this study, made in 2007 in Tenon Hospital, Paris, was to evaluate the percentage of the prescriptions conform with RBU and the analysis of the other different prescriptions in regards to Thésaurus national de cancérologie digestive (TNCD). We found out that 25% of the anticancer prescriptions for digestive tumours in Tenon hospital are not known by the law of "Good Use". Half of these percentages were clearly recommended via the TNCD. The other half of these non-conform prescriptions were realized in an advanced disease in which there were no clear recommendations or references and there were no other choice. The TNCD validation by the National Cancer Institute can reduce the prescriptions, which are considered as non-conform. In the other hand, for the uncertain prescriptions (non-conform), the decision must be systematically discussed in multidisciplinary stuff with detailed argumentations and clear written explications in the medical file.

Digestive endoscopy, including endoscopic ultrasound, plays actually an important role in oncology concerning early diagnosis, tumor staging, and therapeutic procedures. Indeed, improvement of endoscope and dedicated accessories allow to increase applications of therapeutic endoscopy in oncologic indications : curative resection of early carcinoma ant submucosa tumor ; palliative treatment of tumoral bilio-digestive obstruction. Possibilities to resect sessile or flat polyps allow to treat curatively well-differentiated carcinoma without infiltration of the muscularis mucosae, the risk of lymph nodes invasion being null in this cases. In case of invasion of muscularis mucosae, this risk is inferior to 1% for colorectal cancer when submucosal invasion do not exceed 1000 microm but this risk is between 6 and 22% in case of oeso-gastric carcinoma invading the third part of the submucosa. Mortality of endoscopic resection was null in almost published series. Morbidity was 15-20% for colorectal resection with 5-6% of severe complications and up to 23% after oesophageal tumor ablation. Moreover, improvement of echoendoscope dedicated to therapeutic procedures allow from now to achieve non-anatomic pancreatic or biliary drainage through the gastric wall when the retrograde route is not suitable (whipple resection, duodenal stricture) or when drainage of the left hepatic lobe is difficult via the retrograde approach. The aim of this technique is to realize an anastomosis between the left hepatic duct and the stomach. Permanence of this fistula is ensured by insertion of one or two stent. Efficacy and safety of this procedure were recently retrospectively evaluated with a technical success in 91% of cases. Therapeutic endoscopy made many progress during the last years and development of new generation of endoscope and accessories would allow a real endoluminal surgical approach for superficial tumor, bilio-digestive anastomosis or gastro-enteroanastomosis by example.

Gemcitabine is a well-tolerated anti-tumour drug with broad-spectrum activity. It is now recommended for treatment in an increasing number of tumours. Locally advanced or metastatic pancreatic cancer is the only digestive cancer for which it has yet been approved. Numerous phase III trials have addressed gemcitabine's dosage, infusion modalities, and its potential association with other anti-tumour drugs in pancreatic cancer. Standard recommended treatment for this disease in 2006 is gemcitabine monotherapy following Burris'protocol, that is 1000 mg per square meter in a 30 minute-infusion weekly for seven weeks, one week off and then weekly for three weeks, repeated every 4 weeks. Many phase I or II trials have been carried out in all other digestive cancers. They show gemcitabine's potential activity, especially in esophageal cancer, biliary tract adenocarcinoma and hepatocellular carcinoma. Nevertheless, larger studies are required to confirm this efficacy. The aim of this review is to describe the trials that have contributed to determine gemcitabine's infusion modalities in pancreatic cancer. We will then present the studies that have been carried out in other digestive cancers.

Anemia is frequent in cancer patients, is the result of decreased erythropoietin production. In fact in cancer, alteration of immune system alters iron metabolism and inhibits erythropoietin production. In this study we proposed to determine the profile of erythropoietin secretion in anaemic cancer patients in the pre and postoperative period. Our prospective study from January to March 2005 included 41 anemic cancer patients from 30 to 79 years old and 31 healthy individuals with iron deficiency anemia. A measure of erythropoietin, CRP, ferritin, iron levels and hemoglobin were released in healthy individuals and in cancer patients in preoperative period (J0) and postoperative period (J3, J8, J21). In preoperative period, the increase of serum erythropoietin was significantly lower in patients than in healthy individuals. In postoperative period, the levels of erythropoietin at J3 and hemoglobin's at J8 and J21 were significantly higher than in preoperative period (J0) (p0.05). In conclusion, despite the presence of inflammatory syndrome caused by surgery, cancer patients with anaemia increase their erythropoietin production in immediate postoperative period.

All the retrospective and prospective studies concerning IORT in tumors of the digestive tract tend to substantiate a significant improvement in local control without a significant increase in survival. Improvements in the results of IORT can be expected in the near future, and may occur on several fronts: - Technological improvements: advances in the development of IORT machines, with the construction of electron accelerators specifically designed for IORT; greater precision in the systems of collimation (asymmetric collimator, multiple leaves, computerization of the control of collimation); and increased adaptability of the localizers to each clinical situation and to each patients. - Increase in the biological effects of IORT: determination of the exact role of IORT in relation to other therapeutic methods, its integration into the global therapeutic strategy for cancer, and the optimization of IORT doses should all be studied in phase II and III trials. Interesting results are expected from the combination of different methods of preoperative, intraoperative, and postoperative radiotherapy with chemotherapy; the cumulative effect of radiosensitization and cytotoxicity can bring about both local control and treatment of the general disease. In addition, the combination of hypoxic cell radiosensitizers and IORT, a source of important cellular hypoxia as a result of single doses, appears promising. - Lastly, randomized studies in a larger number of patients with objectives and methodologies to be perfected will document the actual contribution of IORT to an increase in survival as part of an overall treatment strategy for digestive tumors. At present, the prognosis remains significantly related to systemic metastatic evolution; this can only be influenced by chemotherapy, whose efficacy remains to be demonstrated. As means for better control of systemic disease are discovered, the clear benefits of local control via IORT will assume increased importance.

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is a scintigraphic imaging technique undergoing a rapid growth in the field of oncology. The constant progress of the detectors, either CDET or PET dedicated cameras, allows to obtain in routine conditions images with a 5 mm spatial resolution. Absolute tracer uptake quantification is also possible, which allows to evaluate objectively therapy efficacy. The mechanisms of FDG tissular accumulation are now better understood. Increase of glycolysis and of transmembrane transport of glucose seems to be at the origin of the high tumorous accumulation of FDG. The main current oncologic application of FDG PET is the diagnosis of malignancy of the isolated pulmonary nodules, with a sensitivity of more than 95%, and in the staging of lung cancer where PET shows higher performances than conventional imaging. The same stands in cutaneous melanoma and for malignancies of the digestive tract, either in colorectal, pancreatic or esophageal localizations. In colorectal cancers, the role of PET has for long being recognized in the differential diagnosis between recurrence and postoperative fibrosis. In the head and neck tumors, FDG also allows to differentiate between recurrence and postradiation necrosis. In lymphoma, the most suitable site for biopsy can be identified on a PET scan and therapy efficacy can also be assessed. In breast cancer, the detection of metastases seems to be possible with FDG. In brain and thyroid cancers, the role of FDG PET remains to be further determined. The low uptake of FDG in prostate cancer metastasis is not in favor of its use in this indication. In conclusion, the indications of FDG PET in oncology are now becoming more precise and it can be expected that clinical PET centers will soon appear in France.

Irinotecan (CPT11), a topoisomerase I inhibitor, is a new cytotoxic agent with a broad spectrum of clinical activity. Two main schedules have been studied and produce similar activity and side-effects: the "european" one--350 mg/m2 every 21 days-, and the "japanese-north american" one where CPT11 is given at a weekly dose of 100-120 mg/m2 for 4 consecutive weeks followed by a 2 week rest period. Activity was initially characterized in advanced colorectal cancers; response rates, disease free-survival and overall survival were 11%, 7-10 months and 8-11 months in patients failing fluoropyrimidine based chemotherapy--statistically improved as compared to best supportive care and infusional fluorouracil-, and 20-30% in patients not previously treated. An interesting activity with response rates of 20-22% (increased to 65% in combination with CDDP) has been shown in relapsed cervix carcinomas; in gastric carcinomas response rates of 20% have been shown, reaching 48% in combination with CDDP. Response rates of 20-22%, increased to 40-60% when irinotecan was associated to CDDP have been reported in non small cell lung cancer and esophagal carcinomas. Further studies are needed for other GI tract cancers, ovarian and head and neck carcinomas while minimal or no clinically meaningful activity has been reported in advanced breast cancer, and haematological malignancies. Irinotecan can be combined to fluoropyrimidines, raltitrexed, cisplatin, carboplatin and oxaliplatin, to gemcitabine, etoposide, vinorelbine and taxanes with flexible schedules (weekly, every 2 weeks, every 21 days. Most of these combinations have an additive or supra additive activity. Its mechanism of action, the spectrum of activity and the acceptable risk-benefit ratio point to irinorecan as a major advance in the field of cytotoxic anticancer therapy.

Male breast cancer represents about only 1% of all breast cancers. We have analysed a retrospective, multicentric series of 404 patients, initially non-metastatic, with mean age of 63 years. The 5 and 10-year overall survival rates were 65 and 36% respectively. Sixty-eight patients developed secondary cancer. From ten patients who already presented with cancer (2.5%) 3 cases corresponded to prostatic cancer treated by estrogen. Four had synchronous cancer (1%). Three and eight patients respectively had a synchronous and metachronous contralateral breast cancer (2.7% of bilateral cancer). Forty-three other patients (10.6%) developed metachronous cancer. The main tumor types were: prostate (9), lung (6), colon and rectum (6), esophagus (4). Four patients developed various hematologic malignancies and 14 patients, various types of solid tumors. From these 43 patients, 27 died; 19 as a result of secondary cancer. This represents 9% of all deaths among the 404 patients. While the bilateral cancer rate is similar to women, the second cancer rate appears to be higher in men. From hematological malignancies, chemotherapy and radiotherapy do not seem to contribute to this high incidence of second cancer.

Somatostatin octapeptide analogues have a longer half-life and are more potent than natural somatostatin (SS-14). Somatostatin analogues are presently approved for the treatment of gastrointestinal (GI) endocrine cancers such as carcinoids, vipomas and glucagonomas. They are also effective in the treatment of inoperable or relapsing acromegaly. Although symptomatic relief is marked and rapidly induced, the inhibitory effect on tumor growth is modest. However, prolonged stabilizations are frequent. Somatostatin analogues may have wider therapeutic indications. Somatostatin octapeptide analogues are also known to interact with growth factors such as epidermal growth factor and insulin-like growth factor, and have shown cytostatic activity in vitro and in vivo in various experimental models of breast, prostate, lung and GI cancers. Neuroendocrine tumors often express somatostatin receptors. Labelled analogues may be useful for tumor assessment and for the prediction of tumor response to therapy. The role of somatostatin analogues in the treatment of the most frequent cancers is currently under investigation.

The inverse relationship between allergic diseases, particularly bronchial asthma, and cancer has been much debated these past years. This inverse relationship may be due to different levels of blood and tissue histamine, and its effect on lymphocytes with H2 receptors. A clinical study was performed on circulating histamine-bearing T cells and on in vivo and in vitro immune response to PPD and histamine in patients with a newly diagnosed digestive neoplasm and in patients with allergic bronchial asthma. The mean percentage of T lymphocytes with histamine receptors was significantly decreased in patients with digestive neoplasm and with allergic bronchial asthma as compared to healthy controls.

We have studied and compared the 1,25-dihydroxyvitamin D3 receptor (RD3) content of 154 human digestive carcinoma with the normal mucosa one, removed at distance from the same surgical specimen. The distribution of biopsies is as follows: 5 oesophagus, 10 stomach, 6 small bowel, 35 right colon, 47 left colon, 40 rectum and 11 pancreas. RD3 were measured by the Dextran Coated Charcoal method and characterized by sucrose gradient ultracentrifugation. One single class of high affinity binding sites (kD = 1.5 +/- 0.7 x 10(-10) M) was defined, with a sedimentation coefficient of approximately 3.4 S. The RD3 was present in the 6 samples of small bowel and in 82% of whole normal mucosa, whatever their localization along the digestive tract and pancreas, while in the tumoral tissue, the RD3 was positive in only 32% of the cases. In these tumor specimens the incidence decreases from 64% in the right colon to 27% in the left colon and only 15% in the rectum (P less than 0.001). RD3 rates vary slightly with the localization and are of the same level in normal tissues and in tumors: 10-314 (median = 59) vs 13-175 (median = 64) (P greater than 0.005) respectively. No significative variations relating to age or sex of patients were found. However, all RD3 positive tumors from left colon and rectum were well differentiated histologically. These results show that the normal colonic mucosa is a potential target for 1,25-dihydroxyvitamin D3, which can play a role in the metabolism of calcium and other ions. They also suggest that vitamin D3 could be a modulator of colorectal cell growth and differentiation and its receptor is frequently lost during malignant transformation.

We report a prospective study concerning the association of surgery-chemotherapy and radiotherapy in the treatment of primary high grade digestive non-Hodgkin's lymphomas in 19 patients. The analysis of 11 stages IE, 5 stages II1E and 3 stages II2E allowed us to evaluate the efficacy and the tolerance of this triple therapeutic association. Fifteen patients are alive and well with a median follow-up of 54 months. One of these patients relapsed, but after autologous bone marrow transplantation is in second unmaintained complete remission. Four patients died of intercurrent aetiology although one death was related to treatment morbidity. Our results and the analysis of literature data lead us to recommend the triple association in the treatment of stage II2E high grade primary digestive lymphomas (PDL) and for PDL without complete resection. However, surgery and chemotherapy appear to be sufficient in the treatment of stages IE and II1E with complete resection.

One hundred and thirteen patients with advanced squamous cell cancer of the head and neck were entered into a multicenter trial. Median age was 54 yr (range: 33-74 yr). Median Karnofsky index was 70 (60-100). Thirty-five patients had had prior induction chemotherapy. The first schedule was carboplatin 300 mg/m2, dl and fluoro-uracil 1000 mg/m2/d administered in continuous IV infusion for 96 h every 4 weeks (group 1). The second schedule was carboplatin 350 mg/m2, dl and fluoro-uracil administered at the same dose every 3 weeks (group II). Median number of cycles was 3 (range: 1-16). Seven patients were not eligible. The response rate was 26% (95% confidence limits: 18-34). Nine patients had a complete response. The median duration of response was 6 months (2-16+). The response rates in the 2 groups were not statistically different (21 and 31%) but disease progression was more frequent in group I (61%) than in group II patients (25%). Six early deaths occurred, without sign of drug toxicity. Grade 2 hematological toxicity between or before any cycle was more frequent in group II patients, in particular for leucopenia (13 vs 42%, P less than 0.05). One death was related to granulopenia. Grade 2 or 3 gastric toxicity was observed in 43 patients. No other major toxicity was observed. In our study, combination therapy with carboplatin and fluoro-uracil was found to be moderately active but myelotoxic.

Multiple Endocrine Neoplasia type 2b (MEN 2b) is a rare syndrome. The principal features are: medullary thyroid carcinoma (MTC), dysmorphism, a ganglioneuromatosis and pheochromocytomas. Eight cases of MEN 2b have been observed at the Institute Gustave Roussy, between 1968 and 1983. Seven involved children under 15 years of age. Eight had a bilateral MTC; six had dysmorphism; six had mucosal tongue neuromas. Six were troubled with visceral ganglioneuromatosis of whom two had intestinal obstruction and one urinary chronic retention. One patient had pheochromocytoma with hypertension. From this experience and other data it appears that: the dysmorphism is frequently poorly interpreted; the visceral ganglioneuromatosis is an early and severe feature; it is important to examine the patient for pheochromocytoma; the MTC must be detected by calcitonin dosage after stimulation, and requires total thyroidectomy; familial screening must be done. To improve the poor prognosis of MEN 2b, early diagnosis and aggressive treatment are necessary.

Two 131-Iodine radiolabelled monoclonal antibodies were used to perform tomoscintigraphy in 42 patients: 11 patients bearing medullary thyroid cancers and 19 patients bearing gastrointestinal cancers received an antibody directed against carcino-embryonic antigen; 12 patients bearing gastro-intestinal cancers received an antibody directed against a non circulating antigen expressed by human colorectal cancers cell lines. Tomoscintigraphy is particularly useful for analysing the complex biodistribution of radiolabelled antibodies and the low contrast images encountered in immunoscintigraphy; the problems related to the true positive rate and to the clinical specificity of the method are discussed.

The authors set out in detail the conditions for which adjuvant chemotherapy is used in the treatment of carcinomas of the upper respiratory and digestive tracts. The conditions are at the same time of a theoretical (natural history as shown by cell kinetics) and of a practical (general physical state) nature. They evaluate 34 randomised therapeutic trials and 14 phase II trials: chemotherapy given either before, during or after radiotherapy. They finally draw several conclusions concerning the use of adjuvant chemotherapy.

The labelling index (LI) of 96 breast adenocarcinomas and of 43 upper respiratory and digestive tract cancers has been measured. For the two histological groups, the distribution of individual values is found to be log-normal, with a mean value depending on the tumour type. Our data have been compared with other authors results. The dispersion of individual values within a same histological type suggests that the LI is interesting as an individual value depending on the patient and his own cancer. For breast adenocarcinomas the LI values obtained have been separated in two groups depending upon the patient age, the age of 53 has been chosen to separate premenopausal from post-menopausal patients. A test of significance showed that the two corresponding log-normal distributions were different, even at the 0.01 level of significance, a mean LI value thus characterizing each distribution.

New regimens of chemotherapy in previously untreated squamous cell head and neck carcinoma yielded a 60 per cent rate of regression in over 50 per cent of patients. Planned radical surgery may be delayed and curative irradiation is often preferred. However, many patients have been excluded for polychemotherapy because of poor general condition. The results of simultaneous perioperative chemotherapy and X-ray therapy are not well known. Adjuvant chemotherapy after initial treatment is difficult to apply and to appreciate for results. Chemotherapy of recurrences is disappointing, even if efficient. Randomised trials are necessary to improve our knowledge in this field.

Incidence rates of the cancer registry of the department of Calvados were compared, by site and by age group, with those obtained from the cancer registry of the comprehensive cancer center in Caen, concerning the population of the department of Calvados. In males, these rates are approximately similar for head and neck sites; for the hospital registry they are 50% of those recorded by the population registry for lung cancer, and 30% for prostatic cancer. In females, the all-sites rates are nearly identical for the youngest age groups and 50% for the older. They are not significantly different for digestive cancer, and 75% for cervix and breast cancer. The incidence rates of both registries were compared with mortality rates. They indicate mortality rates which appear relatively high for the pancreas, and they show imprecisions for the uterus and head and neck (pharynx-larynx) sites.